New Publications in HIV : Archive

20 April 2009

Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa.

Lawn SD et al. AIDS 2009;23:335–42. Jan Observational community-based study to determine the relationship between mortality risk and the CD4 cell response to ART.

High mortality in the first year of ART was related to the proportion of time with CD4 cell counts < 200 cells/μL.

Conclusions: CD4 cell counts are the variable most strongly associated with mortality risk during ART. National HIV programmes in resource-limited settings should be designed to minimize the time patients have CD4 cell counts <200 cells/μL. Link 23 April 2009

The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.

Lima VD et al. J Acquir Immune Defic Syndr 2009 Feb 13. [Epub ahead of print] • This study investigated the impact of longitudinal adherence on survival in drug-naïve individuals starting HAART.
• Non-adherence over time (<95%) was strongly associated with a higher risk of mortality (HR: 3.13; 95% CI: 1.95–5.05).
• Conclusions: Incomplete adherence to HAART over time was strongly associated with increased mortality. Non-adherent patients on EFV-based NNRTI therapies had a higher risk.
Link 28 April 2009

Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care.

Lemly DC et al. J Infect Dis 2009 Feb 16. [Epub ahead of print] • This retrospective cohort study examined all-cause mortality among HIV patients in care on HAART to investigate possible race and sex differences.
• After adjustment for baseline characteristics, death was associated with a number of factors including black race (HR 1.33; p=0.04) and female sex (HR 1.53; p=0.007).
• Conclusions: Race-associated differences in mortality probably resulted from HAART use. Women had an increased mortality risk even after adjustment for HAART use.
Link 06 May 2009

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

Antiretroviral Therapy Cohort Collaboration (ART-CC) Clin Infect Dis 2009;48:1138–51. • This study investigated differences in mortality following individual AIDS-defining events (ADEs) among patients starting combination ART.
• The greatest mortality HR was associated with non-Hodgkin’s lymphoma (HR 17.59; 95% CI 13.84–22.35) and progressive multifocal leucoencephalopathy (HR 10.0; 95% CI 6.70–14.92).
• Conclusions: Mortality rates subsequent to an ADE are dependent on the specific diagnosis
Link 07 May 2009

The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.

Lima VD et al. J Acquir Immune Defic Syndr 2009;50:529–36. • This study investigated the impact of longitudinal adherence on survival in drug-naïve individuals starting HAART containing EFV, NVP, or RTV-boosted ATV or LPV.
• Individual adherence decreased significantly over time and non-adherence over time (<95%) was strongly associated with a higher risk of mortality (HR: 3.13; 95% C): 1.95–5.05). Non-adherent (<95%) patients on NNRTI-based and boosted PI-based regimens were 3.61 (95% CI: 2.15–6.06) and 3.25 times (95% CI: 1.63–6.49), respectively, more likely to die than adherent patients.
• Conclusions: Incomplete adherence to HAART over time was strongly associated with increased mortality. Non-adherent patients on EFV-based HAART were at particularly high risk.
Link 05 June 2009

Comparison of CD4 cell count, viral load, and other markers for the prediction of mortality among HIV-1-infected Kenyan pregnant women.

Brown ER, Otieno P, Mbori-Ngacha DA et al. J Infect Dis 2009;199:1292–1300 • This study investigated the usefulness of CD4-cell count, CD4-cell percentage (CD4%), HIV-1 load, total lymphocyte count (TLC), BMI and haemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of women in Nairobi, Kenya.
• Mortality rates at 1 and 2 years postpartum were 2.1% (95% CI: 0.7–3.4%) and 5.5% (95% CI: 3.0–8.0%), respectively. CD4-cell count and CD4% had the highest AUC value (>0.9). BMI, TLC and haemoglobin were each associated with but poorly predictive of mortality (positive predictive value <7%). The HIV-1 load did not predict mortality beyond the CD4-cell count.
• Conclusions: The CD4-cell count and CD4% measured during pregnancy were useful predictors of mortality among pregnant women. TLC, BMI, and haemoglobin had limited predictive value. The HIV-1 load did not predict mortality any better than the CD4-cell count alone.
Link 05 June 2009

Monitoring HIV treatment in resource‐limited settings: reassuring news on the usefulness of CD4+ cell counts.

Fowler MG, Owor M. J Infect Dis 2009;199:1255–7. • This study investigated the usefulness of CD4-cell count, CD4-cell percentage (CD4%), HIV-1 load, total lymphocyte count (TLC), BMI and haemoglobin measured at 32 weeks’ gestation as predictors of mortality in a cohort of women in Nairobi, Kenya.
• Mortality rates at 1 and 2 years postpartum were 2.1% (95% CI: 0.7–3.4%) and 5.5% (95% CI: 3.0–8.0%), respectively. CD4-cell count and CD4% had the highest AUC value (>0.9). BMI, TLC and haemoglobin were each associated with but poorly predictive of mortality (positive predictive value <7%). The HIV-1 load did not predict mortality beyond the CD4-cell count.
• Conclusions: The CD4-cell count and CD4% measured during pregnancy were useful predictors of mortality among pregnant women. TLC, BMI, and haemoglobin had limited predictive value. The HIV-1 load did not predict mortality any better than the CD4-cell count alone.
Link 25 June 2009

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial.

Zolopa AR, Andersen J, Komarow L et al. PLoS ONE 2009;4:e5575. • This clinical trial (ACTG A5164) compared early ART (given within 14 days of starting treatment for acute opportunistic infections) with deferred ART (given after treatment for acute opportunistic infection was completed).
• Early and deferred ART started a median of 12 and 45 days after starting treatment for acute opportunistic infections, respectively.
• The difference in the primary endpoint was not statistically significant: AIDS progression/death, 14% versus 24%; no progression but with incomplete viral suppression, 38% versus 31%; and no progression with optimal viral suppression, 48% versus 45% for early versus deferred treatment (p=0.22).
• However, early ART was associated with fewer AIDS progression/deaths (OR: 0.51; 95% CI: 0.27–0.94), a longer time to AIDS progression/death (HR: 0.53; 95% CI: 0.30–0.92), a shorter time to achieving a CD4 count >50 cells/mL (p<0.001) and no increase in adverse events.
• Conclusions: These results support the early initiation of ART in patients presenting with acute AIDS-related opportunistic infections.
Link 07 December 2009

Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.

Deeks SG et al. Clin Infect Dis 2009;49:1582–90. • This study used Multivariate Cox regression to assess the factors associated with time to second regimen failure and time to death after the onset of second regimen failure in patients who experienced VF (defined as an HIV RNA level >1000 copies/mL), received modified therapy and then had a second episode of VF.
• Of 42,790 patients who received therapy, 7,159 experienced a second VF. The risk of second VF decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; p<0.001). The cumulative mortality after onset of second VF was 26% at 5 years and decreased over time.
• A history of AIDS, a lower CD4+ T-cell count and a higher plasma HIV RNA level were each independently associated with mortality.
• Conclusions: Mortality rates for those who have experienced failure of two or more regimens have remained high. Plasma HIV RNA levels, CD4+ T-cell counts at time of treatment failure and a history of AIDS remain independent risk factors for death. These factors remain important targets for those in need of more aggressive therapeutic interventions.
Link 22 April 2010

Late diagnosis in the HAART era: proposed common definitions and associations with mortality.

UK Collaborative HIV Cohort (UK CHIC) Steering Committee. AIDS 2010;24:723–7. • This observational cohort study attempted to define a presentation after clinical or immunological disease progression that would reliably identify patients at high risk of mortality during the first 3 months after HIV diagnosis.
• Two immunological (CD4 cell count <200 cells/mm3 and <50 cells/mm3) and two clinical (AIDS and severe/moderate AIDS) criteria for presentation with advanced HIV disease were compared.
• The predictive ability of each diagnosis for identifying individuals who died in the first 3 months after HIV diagnosis was assessed.
• Sensitivities of the individual criteria ranged from 18.0% (severe/moderate AIDS) to 50.5% (CD4 cell count <200 cells/mm3) with specificities ranging from 73.5% (CD4 <200 cells/mm3) to 97.8% (severe/moderate AIDS).
• Combinations of clinical and immunological criteria increased the sensitivity but decreased the specificity.
• Conclusion: Presentation with 'advanced HIV disease' was defined as a CD4 cell count <200 cells/mm3 or AIDS and 'late' presentation was defined as a CD4 cell count below that when treatment should be initiated (currently <350 cells/mm3) or AIDS.
Link 07 June 2010

Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies.

Clin Infect Dis 2010;50:1387–96. • This study investigated the specific causes of mortality and the associations of prognostic factors with cause-specific mortality among 39,272 HIV+ patients in 13 cohorts who started ART in Europe or North America from 1996–2006.
• In 1597 of 1876 deaths (85%), where a definitive cause of death could be assigned, 792 (49.5%) were AIDS related, 189 (11.8%) were due to non-AIDS malignancies, 131 (8.2%) to non-AIDS infections, 124 (7.7%) to violence- and/or drug-related causes, 113 (7.0%) to liver disease and 103 (6.5%) to cardiovascular disease.
• Rates of AIDS-related death (HR per 100 cell decrease: 1.43; 95% CI: 1.34–1.53) and death from renal failure (HR: 1.73; 95% CI: 1.18–2.55) were strongly inversely related to CD4 count at initiation of ART.
• Rates of death attributable to AIDS (HR for VL >5 vs 5 log copies/mL: 1.31; 95% CI: 1.12–1.53), infection (HR: 1.85; 95% CI: 1.25–2.73), cardiovascular (HR: 1.54; 95% CI: 1.05–2.27) and respiratory causes (HR: 3.62; 95% CI: 1.30–10.09) were higher in patients with baseline VL >5 log copies/mL than in other patients.
• The proportion of deaths classified as AIDS related decreased with increasing duration of ART.
• Conclusions: Important contributors to non-AIDS mortality in treated HIV+ patients must be addressed if reductions in mortality rates are to continue.
Link 07 June 2010

Decline in early life mortality in a high HIV prevalence rural area of South Africa: evidence of HIV prevention or treatment impact?

Ndirangu J et al. AIDS 2010;24:593–602. • This retrospective study investigated the temporal and spatial associations between early life mortality rates and a prevention of mother-to-child transmission (PMTCT) programme (single-dose NVP), an HIV treatment programme and maternal HIV in a largely rural population with a high prevalence of antenatal HIV.
• Mortality was independently associated with birth season (adjusted HR: 1.16; 95% CI: 1.02–1.33), maternal education (HR: 1.21; 95% CI: 1.02–1.43), maternal HIV (HR: 4.34; 95% CI: 3.11–6.04) and ART availability (HR: 0.46; 95% CI: 0.33–0.65).
• Children born at home (unlikely to have received PMTCT) had a 35% higher risk of dying than children born in a facility where PMTCT was available (HR: 1.35; 95% CI: 1.04–1.74).
• Conclusions: The results confirm the importance of maternal survival and show the importance of the PMTCT and maternal HIV treatment in improving the survival of their young children.
Link 25 June 2010

Body mass index and risk of tuberculosis and death.

Hanrahan CF et al. AIDS 2010;24:1501–8. • This study investigated the effect of BMI on all-cause mortality and TB incidence among a cohort of HIV+ adults in Soweto, South Africa.
• Mortality rates (per 100 person-years) were 10.4 for baseline BMI of ≤18.5, 3.6 for baseline BMI 18.6–25, 1.7 for baseline BMI 25.1–30 and 1.6 for baseline BMI >30.
• Compared to those with normal BMI, overweight (adjusted HR: 0.59; 95% CI: 0.40–0.87) and obese (adjusted HR: 0.48; 95% CI: 0.29–0.80) individuals had a significantly reduced mortality risk and
• Incidence rates (per 100 person-years) of TB by baseline BMI were 7.3 for underweight, 6.0 for normal, 3.2 / for overweight and 1.9 for obese.
• Compared to those with normal BMI, those with overweight (adjusted HR: 0.56; 95% CI: 0.38–0.83) and obese BMI (adjusted HR: 0.33; 95% CI: 0.19–0.55) were at a significantly reduced risk of developing TB.
• Conclusion: HIV+ individuals with an obese or overweight BMI have a significantly reduced risk of both mortality and TB after adjusting for HAART use and CD4 cell count.
Link